The tricyclic antidepressant agents are widely used in the treatment of mental illness. Unfortunately, a major risk in treating depressed patients with these agents is that of prescribing potentially toxic drugs to individuals who are very likely to ingest an overdosage in attempts at suicide. Clinically, physostigmine is known to be highly effective in antagonizing the central nervous system manifestations of tricyclic-induced toxicity; however, considerable controversy exists on the use and purported effectiveness of the anticholinerase agent in protecting against the cardiotoxicity produced by an overdosage of the tricyclic antidepressants. The objectives of this investigation are to (1) characterize and study the mechanism(s) of the cardiotoxic actions of the tricyclic antidepressants, (2) study various drugs as possible antidotes for the cardiotoxicity produced by the tricyclics and study the mechanism of any protective action observed and (3) compare the toxic actions produced by the tricyclics with that of cocaine, quinidine, atropine and other agents. These studies will be performed in several animal species including cat, dog, rabbit, and guinea pig.